Gene therapy somatic

A further committee. The Committee for Advance Therapies, is to be established under regulation (EC) No. 1394/2007 to deal with issues raised by emerging drug products based on gene therapy, somatic cell therapy and tissue engineering. 

The Competent Authorities are allowed a maximum of 60 days to review the data, or 90 days in the case of trials involving medicinal products for gene therapy, somatic cell therapy (including xenogeneic cell therapy), and all medicinal products containing genetically modified organisms. Such trials require written authorisation from the Competent Authority as distinct from other types of product where the authorities may just notify the sponsor of the acceptability (no-objection) of the application. If issues are raised, the sponsor may amend the application once, with a consequent extension to the allowed review period. 

Uses of cloned genes Produce recombinant proteins Gene therapy (somatic) Transgenic animals (germ line) Produce cDNA probes for blots... 

A common clinical trial application form will be used and will be accompanied by data on the Quality, Safety, and Efficacy of the IMP to the CA. The application process is an implicit approval within a maximum 60-day review period with one exception, for clinical trials with biotechnology IMPs, e.g., gene therapy, somatic cell therapy, and genetically modified organisms. In this case, written approval is mandatory and a 90-day review period will apply. 

FDA. (1996). Points to Consider in Human Somatic Cell Therapy and Gene Therapy. 

Kessler, D., Siegel, J., Noguchi, P, Zoon, K., Feidon, K. and Woodcock, J. (1993). Regulation of somatic-cell therapy and gene therapy by the food and Drug Administration. New Engl. J. Med. 329 1169-1173. 

FDA (1996) Addendum to the points to consider in human somatic cell and gene cell therapy, Human Gene Therapy 1 1181-1190. 

In somatic cell gene therapy, a DNA sequence is inserted into a somatic cell to correct a mutation. Cells may be removed from the patient for manipulation and subsequent reinsertion (ex vivo therapy), or they may be manipulated without removal fi om the patient (in vivo therapy). Ideally, cells with a very long life span (e.g., bone marrow stem cells) are treated, but other cells (e.g., lymphocytes) are sometimes more practical targets. 

Somatic cell gene therapy involves the use of recombinant DNA techniques to introduce a therapeutic DNA sequence into a somatic (noninherited) cell. 

Currently, more than 400 human somatic cell gene therapy protocols are being tested. Most of these involve the use of genetically modified cells to treat noninherited diseases. For example, normal copies of the p53 tumor suppressor gene are inserted into lung tumors to halt tumor progression, and genetically modified cells have been used to create new coronary vessels in patients with coronary heart disease. Success has also been achieved in the treatment of hereditary disease (most notably, the recent successful treatment of X-linked severe combined immune deficiency see Clinical Correlate). 

Gene therapy is used to correct the effects of a disease-causing mutation. Somatic cell gene therapy is used in humans because the alteration is not transmitted to offspring. Germline gene therapy (not practiced in humans) alters all cells in the body and results in transmission of the alteration to offspring. 

Mhashilkar, A. et al. (2001). Gene therapy — therapeutic approaches and implications. Biotechnol. Adv. 19(4), 279-297. Moller, P. Schadendorf, D. (1997). Somatic gene therapy and its implications in melanoma treatment. Arch. Dermatol. Res. 289(2), 71-77. 

The investigators evaluated the safety of their nonviral somatic-cell gene therapy system, which they call transkaryotic implantation, in six patients with severe hemophilia. The procedure involved isolation of dermal fibroblasts from the patients upper arms. The fibroblasts were then transfected with a factor VIII genebearing plasmid. Cells that expressed factor VIII were cloned, propagated, and implanted into the patients abdomens. This technique can be considered as a less invasive form of ex vivo gene therapy. 

An in vivo model of somatic cell gene therapy for human severe combined immunodeficiency. Ferrari, G., Rossini, S., Giavazzi, R., Maggioni, D., Nobili, N., Soldati, M., Ungers, G., Mavilio, F., Gilboa, E., Bordignon, C. (1991). Science, 251 (4999) 1363-1366. 

Zatloukal K, et al. Somatic gene therapy for cancers the utility of transfer infection in generating tumor vaccines. Gene 1993 135 199-207. 

Artificial chromosomes (Chapter 9) have been constructed as a means of better understanding the functional significance of many structural features of eukaryotic chromosomes. A reasonably stable artificial linear chromosome requires only three components a centromere, telomeres at each end, and sequences that allow the initiation of DNA replication. Yeast artificial chromosomes (YACs see Fig. 9-8) have been developed as a research tool in biotechnology. Similarly, human artificial chromosomes (HACs) are being developed for the treatment of genetic diseases by somatic gene therapy. 

Temin, H.M. (1990) Safety considerations in somatic gene therapy of human disease with retrovirus vectors. Hum. Gene Then, 1, 111-123. 

This approach was effective in that it expressed IL-4 pancreas specifically, without any side-effects from the systemic expression of IL-4. These results also indicated that autoim-mune diabetes in NOD mice is not a systemic disease, and it can be modulated from the islet compartment. Therefore, for somatic gene therapy, the rat insulin pro-moter was inserted upstream of the IL-4cDNA (Lee et al., 2001a). This plasmid, pRIP-mIL-4 was complexed with water soluble lipopolymer and transfected in vitro. The results indicated that pRIP-mIL-4 expressed IL-4 cell-type specifically. 

Piccirillo, C.A., Chang, Y. and Prud homme, G.J. (1998) TGF-/ 1 somatic gene therapy prevents autoimmune disease in nonobese diabetic mice. J. Immunol., 161, 3950-3956. 

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